In human breast cancer, two patient populations seem to exist, one of which experiences a mortality rate ten times greater than the other. Histological differences between the tumors of these two groups may be identifiable in a study of tumors from patients who die within two years of diagnosis vs. those who survive more than ten years. We hypothesize that such reliable histological discriminants can be identified by a quantitative morphometric analysis of differentiation (cell maturation) markers in the primary tumors. Stereological techniques for the analysis of differentiation will be applied to the quantitation of glandular differentiation, nuclear pleomorphism, and a selected group of histochemical markers (cellular products and neoplastic phenotype antigens). Programs for computer storage and analysis of numerical data will be developed. Our ultimate aim is to develop techniques that are sufficiently practical to be used in the routine Surgical Pathology Laboratory, and sufficiently objective to be reproducible.